This laboratory has established that the pattern of T helper cell (Th) dysfunction seen in asymptomatic, HIV-seropositive (HIV+) individuals is also detected in patients with systemic lupus erythematosus (SLE), and in a murine model of SLE that is induced by i.v. inoculation of parental T cells into F1 (P>F1) mice. Certain P>F1 combinations result in an acute graft-vs-host disease (acute GVHD), with parental CD8+ T cells being a dominant population. These CD8+ cells exhibited cytotoxic T lymphocyte (CTL) activity against F1 allo antigens. In contrast, other P>F1 combinations induce a chronic GVHD, in which the dominant cell type is F1 B cells that produce anti-DNA antibodies, and results in a lupus-like condition. We recently discovered one P>F1 model in which there was a natural shift from parental CD8-dominated acute GVHD to F1 B cell-dominated chronic GVHD, accompanied by the disappearance of parental CD8+ T cells and P-anti-F1 CTL. This shift to B cell activity, autoantibody production and an SLE-like condition was associated with the disappearance of CD8+ T cells that could be delayed or prevented by inoculation of parental cells that recognize the alloantigens expressed by the F1 B cells. Experimental autoimmune encephalomyelitis (EAE) was induced in the susceptible SJL/J mouse strain by immunization with the myelin basic protein. Lymph node cells from these immunized mice were inoculated into nanve SJL/J mice, which induces an EAE condition that involves cycles of relapse and remission. Relapse was associated with increased IFN-g. In contrast, remission cycles were immediately preceded by peak levels of indoleamine 2,3-dioxygenase (IDO) detected in neurons but not in other tissue. IDO is an enzyme that catabolizes tryptophan, which is required for T lymphocyte survival. These results raises the possibility that IDO contributes to the remission phases of EAE (and possibly MS) by destroying specific T cells residing in nervous tissue that contribute to this autoimmune condition.